Liposuction is one of the most popular cosmetic surgery procedures currently available. It involves the surgical removal of fat deposits using suction, optionally assisted by solutions to assist in fat removal. Liposuction, also known as lipoplasty or suction lipectomy, reduces fat through an incision in the skin through which a cannula is inserted. Tumescent fluid is injected into the treatment region, then the cannula is inserted. The cannula is connected to a suction source and the unwanted fat is aspirated through the cannula and discarded. Liposuction is performed under general or local anesthesia, depending on the amount and location of the fat to be reduced.
The use of liposuction and/or other surgical methods of fat removal are associated with significant adverse events including temporary bruising, swelling, numbness or hypersensitivity, soreness and burning sensation, risk of infection, and pigmentation changes. Other more serious complications include the formation of fat clots or blood clots, which can migrate to the lungs and cause death; excessive fluid loss, which can lead to shock; fluid accumulation that must be drained; fluid overload leading to congestive heart failure; friction burns or other damage to the skin or nerves; and perforation injury to the vital organs. Additionally, liposuction requires a recovery time of up to 1-2 weeks. Moreover, because surgical procedures such as liposuction require local and occasionally general anesthesia, significant anesthesia-related risks are associated with surgical fat removal.
In 1959, phosphatidylcholine (hereinafter “PC”) was isolated and used intravenously in Odessa, Russia, for the treatment of fat embolism. PC has also been used in treating xanthelasmas in Europe and in South America. An injectable form of PC (LIPOSTABIL®, Sanofi-Aventis, Brigewater, N.J.) has been indicated for treatment of fat embolisms, coronary artery plaque, and fat tissue.
PC is often an ingredient in injectable fat reducing formulas. When isolated, it is produced as a powder. When reconstituted, it is quite viscous and must be mixed with a detergent, such as sodium deoxycholate (hereinafter “DC”), to solubilize it sufficiently to create an injectable form. DC is a bile salt that can function to make the PC soluble in water or other biocompatible solvents; otherwise, the PC can precipitate out of solution. DC has been described as having a “detergent” effect on fat dissolution in a porcine in vitro study and has nonspecific effects on both adipose and muscle cells. Other pharmaceuticals, such as FUNGIZONE® (Bristol Myers Squibb, New York, N.Y.) (an injectable form of amphotericin B), are commonly combined with bile salts to enhance their solubility and make them compatible with intravenous delivery.
While formulations of DC without PC (“DC formulations”) and formulations of PC combined with DC (“PC/DC formulations”) have been shown to achieve a level of fat reduction, substantial unresolved problems remain with the use of such formulations and methods of use, as reported in Duncan et al. (Duncan D. Injection lipolysis for body contouring, p 59-70. Body Contouring, ed. Schiffman and DiGiuseppe, Springer 2010, Berlin.).
While meeting with some success, prior techniques and compositions have met with certain limitations, such as skin loss, drainage of liquefied necrotic fat, excessive fibrosis, injections into muscle causing weakness, nodules, or adhesions with limitation of range of motion, numbness, paresthesias, and marginal mandibular nerve palsy. Therefore it would be desirable to have a method of reducing localized fat deposits that does not require surgery or prolonged recovery time and has fewer adverse side effects than currently available methods.